Regulation of Adipogenesis and Key Adipogenic Gene Expression by 1, 25-Dihydroxyvitamin D in 3T3-L1 Cells

PLoS One. 2015 Jun 1;10(6):e0126142. doi: 10.1371/journal.pone.0126142. eCollection 2015.

Abstract

The functions of 1, 25-dihydroxyvitamin D (1, 25-(OH)2D3) in regulating adipogenesis, adipocyte differentiation and key adipogenic gene expression were studied in 3T3-L1 preadipocytes. Five concentrations (0.01, 0.1, 1, 10, 100 nM) of 1, 25-(OH)2D3 were studied and lipid accumulation measured by Oil Red O staining and expression of adipogenic genes quantified using quantitative real-time PCR. Adipogenic responses to 1, 25-(OH)2D3 were determined on 6, and 12 h, and days 1-10 after induction of adipogenesis by a hormonal cocktail with or without 1, 25-(OH)2D3. In response to 1, 25-(OH)2D3 (1, 10, and 100 nM), lipid accumulation and the expression of PPARγ, C/EBPα, FABP4 and SCD-1 were inhibited through day 10, and vitamin D receptor expression was inhibited in the early time points. The greatest inhibitory effect was upon expression of FABP4. Expression of SREBP-1c was only affected on day 2. The lowest concentrations of 1, 25-(OH)2D3 tested did not affect adipocyte differentiation or adipogenic gene expression. The C/EBPα promoter activity response to 1, 25-(OH)2D3 was also tested, with no effect detected. These results indicate that 1, 25-(OH)2D3 inhibited adipogenesis via suppressing adipogenic-specific genes, and is invoked either during PPARγ activation or immediately up-stream thereof. Gene expression down-stream of PPARγ especially FABP4 was strongly inhibited, and we suggest that the role of 1, 25-(OH)2D3 in regulating adipogenesis will be informed by further studies of adipogenic-specific gene promoter activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / drug effects*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation / drug effects
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression / drug effects
  • Mice
  • Stearoyl-CoA Desaturase / metabolism
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Fabp4 protein, mouse
  • Fatty Acid-Binding Proteins
  • Sterol Regulatory Element Binding Protein 1
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase

Grants and funding

The authors thank the Idaho Experiment Station for support of these studies. The authors also thank the China Scholarship Council for support of Ms. Shuhan Ji.